Cesium carbonate → 1,1-Dimethylethyl 3-methyl-1-(3-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate

Participants

Reaction Steps

A solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (600 mg, 3 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 2-bromo-3-methylpyridine (515 mg, 3 mmol) in 1,4-dioxane (20 ml) was treated with cesium carbonate (1464 mg, 4.5 mmol), Xantphos™ (130 mg, 0.225 mmol) and tris(dibenzylideneacetone)dipalladium(0) (68.6 mg, 0.075 mmol) and the mixture was heated under reflux under argon for 18 hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were combined, washed with water and brine and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 0-100% ethyl acetate in isohexane to give 1,1-dimethylethyl 3-methyl-1-(3-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate (700 mg, 80%). LC/MS [M+H]+=292. (ii) A solution of 1,1-dimethylethyl 3-methyl-1-(3-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylate (700 mg, 2.4 mmol) in TFA/DCM (1:2, 12 ml) was stirred at room temperature for 6 hours. The solution was evaporated and the residue was co-evaporated with toluene and dried to give 3-methyl-1-(3-methyl-2-pyridinyl)-2-oxo-4-imidazolidinecarboxylic acid TFA salt (assume ˜2.4 mmol) which was used in the next step. LC/MS [M+H]+=236.

Provenance & Evidence